Affinity Selections of DNA-Encoded Chemical Libraries on Carbonic Anhydrase IX-Expressing Tumor Cells Reveal a Dependence on Ligand Valence.

DNA-encoded chemical libraries carbonic anhydrase IX cell-based affinity selections code-specific qPCR ligand valence

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
21 Jun 2021
Historique:
received: 04 03 2021
pubmed: 28 4 2021
medline: 29 6 2021
entrez: 27 4 2021
Statut: ppublish

Résumé

DNA-encoded chemical libraries are typically screened against purified protein targets. Recently, cell-based selections with encoded chemical libraries have been described, commonly revealing suboptimal performance due to insufficient recovery of binding molecules. We used carbonic anhydrase IX (CAIX)-expressing tumor cells as a model system to optimize selection procedures with code-specific quantitative polymerase chain reaction (qPCR) as selection readout. Salt concentration and performing PCR on cell suspension had the biggest impact on selection performance, leading to 15-fold enrichment factors for high-affinity monovalent CAIX binders (acetazolamide; K

Identifiants

pubmed: 33905156
doi: 10.1002/chem.202100816
doi:

Substances chimiques

Antigens, Neoplasm 0
Ligands 0
Small Molecule Libraries 0
DNA 9007-49-2
Carbonic Anhydrase IX EC 4.2.1.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8985-8993

Subventions

Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : grant 310030_182003/1
Organisme : Carlsbergfondet
ID : CF18-0132 and CF19-0060

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Sebastian Oehler (S)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Marco Catalano (M)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Ilario Scapozza (I)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Martina Bigatti (M)

Philochem AG, Libernstrasse 3, 8112, Otelfingen, Switzerland.

Gabriele Bassi (G)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Nicholas Favalli (N)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Michael R Mortensen (MR)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Florent Samain (F)

Philochem AG, Libernstrasse 3, 8112, Otelfingen, Switzerland.

Jörg Scheuermann (J)

Department of Chemistry and Applied Biosciences ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.

Dario Neri (D)

Philochem AG, Libernstrasse 3, 8112, Otelfingen, Switzerland.

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